Yang Lan, Ji Yu, Chen Ling, Li Mei, Wu Fei, Hu Jianming, Jiang Jinfang, Cui Xiaobin, Chen Yunzhao, Pang Lijuan, Wei Yutao, Li Feng
Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
PLoS One. 2017 Oct 26;12(10):e0186319. doi: 10.1371/journal.pone.0186319. eCollection 2017.
The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076-2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168-3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286-0.621, p = 8.83×10-6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC.
中国西北部新疆地区的哈萨克族人群中，食管鳞状细胞癌（ESCC）发病率较高。尽管食管癌（EC）的病因尚未阐明，但有报道称其涉及免疫机制。在本研究中，招募了268例哈萨克族ESCC患者和500例年龄及性别匹配的对照者。从患者石蜡包埋的肿瘤标本及对照者外周血淋巴细胞中提取DNA，用于LMP2/LMP7基因分型。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析检测LMP2/LMP7基因单核苷酸多态性（SNP）。我们发现，哈萨克族人群中，LMP2基因杂合R/C基因型和纯合C/C基因型会显著增加ESCC发病风险（LMP2 R/C：OR = 1.470，95%CI = 1.076 - 2.008，p = 0.015；LMP2 C/C：OR = 2.048，95%CI = 1.168 - 3.591，p = 0.011）。相反，LMP7基因杂合Q/K多态性则会降低该人群患ESCC的风险（OR = 0.421，95%CI = 0.286 - 0.621，p = 8.83×10 - 6）。此外，LMP2 R/C + C/C基因型与肿瘤浸润深度增加相关（p = 0.041）。单倍型分析显示，单倍型A（包括野生型纯合LMP2/TAP1和突变型LMP7）会降低哈萨克族人群对ESCC的易感性；相反，单倍型E（包括野生型纯合LMP2/LMP7/TAP1）则是ESCC易感性增加的危险因素。这是首次报道LMP2基因杂合R/C和纯合C/C基因型会增加哈萨克族人群对ESCC的易感性，而LMP7基因杂合Q/K基因型会降低该人群对ESCC的易感性。然而，LMP2和LMP7均与人类乳头瘤病毒（HPV）感染无关。了解LMP2/LMP7基因变异性将为哈萨克族ESCC患者提供新的治疗视角。
